Journal of Alzheimer’s Disease 47 (2015) 319–322 DOI 10.3233/JAD-150097 IOS Press 319 Short Communication A Novel CSF1R Mutation in a Patient with Clinical and Neuroradiological Features of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids Ilaria Di Donato a,1 , Carmen Stabile a,1 , Silvia Bianchi a , Ilaria Taglia a , Andrea Mignarri a , Simona Salvatore a , Elisa Giorgio b , Alfredo Brusco b , Isabella Simone c , Maria Teresa Dotti a and Antonio Federico a,* a Unit Clinical Neurology and Neurometabolic Diseases, Department Medicine, Surgery and Neurosciences, Medical School, University of Siena, Siena, Italy b Department of Medical Sciences, University of Turin, Turin, Italy c Neurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organ, University of Bari, Bari, Italy Accepted 16 April 2015 Abstract. Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant cerebral white matter degeneration leading to progressive cognitive and motor dysfunction. The peripheral nervous system is generally spared. Recently, mutations in the colony-stimulating factor-1 receptor (CSF1R) gene have been shown to be associated with HDLS. Here we report a new case of HDLS, carrying a mutation in CSF1R and manifesting rapidly progressive dementia and peripheral neuropathy. Keywords: CSF1R, HDLS, leukoencephalopathy, presenile dementia INTRODUCTION Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal domi- nant disorder characterized by cerebral white matter degeneration with focal swellings of axons. Since the original HDLS kindred identified in Sweden [1], both hereditary and sporadic cases have been 1 These authors contributed equally to this work. * Correspondence to: Prof. Antonio Federico, Unit Clinical Neu- rology and Neurometabolic Diseases, Department of Medicine, Surgery and Neurosciences, Medical School, University of Siena, Viale Bracci 2, 53100 Siena, Italy. Tel.: +39 0577 585763; Fax: +39 0577 40327; E-mail: federico@unisi.it. described. Onset is usually in the fourth to fifth decade of life. The clinical picture is characterized by behavioral and cognitive changes [2], often associated with unsteady gait, urinary incontinence, seizures, and involuntary movements. Dementia, abulia, dys- phagia, and severe motor dysfunction appear later. Brain magnetic resonance imaging (MRI) shows nonspecific frontotemporal leukoencephalopathy with concomitant cerebral atrophy. Cerebral white matter abnormalities are initially patchy and asymmetri- cal, and later become confluent and symmetrical. Neuropathology shows a loss of myelin and axons, gliosis, and macrophages in the presence of axonal swellings (spheroids) [3]. The peripheral nervous ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved